Case study analysis of reimbursement decisions for medicines with real-world evidence in France

Specific cases from the Haute Autorité de Santé (HAS) study of reimbursement decisions after the presentation of post-registration studies (for more details, see here) were selected for more in-depth analysis. Cases when the reimbursement rate or comparative effect rate was downgraded (resulting in less or no coverage) were examined in order to understand the discrepancies between RCT and real-life post-registration studies.

What was examined?

The medicines examined in-depth were those considered ‘not comparable’ (when the real-life post registration study results were different from RCT data) for the impact on morbidity and mortality and whose actual therapeutic benefit (ACB) or clinical added value (CAV) were downgraded within the last 15 years. The aspects of the PICO framework were used to describe the discrepancies between the post-registration studies and RCT data and to provide some thoughts for future medicine development in similar indications.

What were the findings and conclusions?

Findings

Eight indications that were downgraded were identified for in-depth review. An additional indication with stable ACB/CAV that had ‘comparable’ real-life study and RCT results was also selected for an in-depth study.

One case study showed no discrepancy between real-life and RCT data, while in downgraded cases, real-life results were not ‘comparable’ or aligned with RCT data.

For 5 indications with large populations such as chronic diseases, discrepancies between real-life and RCT data were typically related to the population (in terms of age and comorbidities) and these differences had an impact on the reported safety and efficacy of the medicine.

For 3 orphan indications, discrepancies between real-life data and RCT data were because of differing administration of the treatment and the recruitment to the real-life study which had an impact on the reported outcomes (this may be due to the lack of the healthcare structure to secure implementation and proper use of the new intervention).

For more details of specific cases, see the research briefing [INSERT LINK HERE].

Conclusions

Case studies revealed that the challenges in large indications are to secure representativeness in RCTs versus real practice in terms of population: more pragmatic designs may be useful.

Case studies of orphan medicines seem to support the adaptive pathway approach with a continuum of data collection (using registries or other databases) may be useful.

Funding

The research leading to these results has received support from the Innovative Medicines Initiative Joint Undertaking under grant agreement no [115546], resources of which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7/2007-2013) and EFPIA companies in kind contribution.